a. Field of the Invention
This invention relates to thiophene ethanolamines, to processes for their preparation and to intermediates therefor.
More specifically, the compounds of this invention are thiophene ethanolamines characterized further in that they are substituted on the nitrogen atom with an alkyl or an aralkyl radial and are optionally substituted on the thiophene portion.
B. Description of the Prior Art
The prior art relating to thiophene ethanolamines is rather niggardly. An early report by C. F. Heubner, et al., J. Org. Chem., 18, 21 (1953), described the preparation of the thiophene ethanolamine, .alpha.-(aminomethyl)thiophene-2-methanol, which was found to have pressor activity. In 1968, E. D. Bergmann and Z. Goldschmidt, J. Med. Chem., 11, 1121 (1968), described soem corresponding N-alkyl derivatives of the latter thiophene ethanolamine, noting that these derivatives possessed no significant pharmacologic activity. A still more recent report, C. Carrol, et al., J. Med. Chem., 16, 882 (1973), described a related series of N-substituted thiophene ethanolamines, the substitution being alkyl, phenyl or such that the nitrogen atom forms part of a pyrrolidine, piperidine or morpholine ring. A variety of pharmacologic properties properties were reported for the series including the property that they antagonized the hypotensive response to isoproterenol.
Unexpectedly, we have found that the compounds of the present invention, and particularly the N-(aralkyl)-thiophene ethanolamines are potent antihypertensive and .beta.-receptor blocking agents. These properties together with their relatively low toxicity and the direct manner in which these compounds are prepared render them useful and practical for the treatment of hypertensive conditions and lessening undersirable .beta.-adrenergic stimulation of the myocardium.